Microtubule-associated protein 1 light chain 3 is a fibronectin mRNA- binding protein linked to mrna translation in lamb vascular smooth muscle cells

Bin Zhou, Nancy Boudreau, Claire Coulber, James Hammarback, Marlene Rabinovitch

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Intimal cushions form in the fetal ductus arteriosus by fibronectin- dependent smooth muscle cell migration which is associated with greater efficiency of fibronectin mRNA translation. We investigated whether the AU- rich element (ARE), UUAUUUAU, in the 3'-untranslated region (3'UTR) of fibronectin mRNA is involved in this mechanism by transfecting smooth muscle cells with plasmids containing the chloramphenicol acetyltransferase coding region with its 3'UTR replaced by fibronectin 3'UTR bearing intact or mutated ARE. More efficient translation of fusion mRNA with intact versus mutated ARE was observed. This effect was amplified in ductus (10.9-fold) compared with nonmigratory, lower fibronectin-producing aorta cells (6.5-fold). Ductus cells transfected with wild-type but not ARE-mutated plasmid reverted to the stellate phenotype of aorta cells associated with reduced fibronectin production. This suggested that plasmid ARE sequesters RNA-binding factors, thereby reducing endogenous fibronectin mRNA translation. We next purified a 15-kD fibronectin ARE-dependent RNA-binding protein and identified it as microtubule-associated protein 1 light chain 3 (LC3). LC3 is present in greater amounts in ductus compared with aorta cells, and overexpression of LC3 in aortic cells by transfection enhances fibronectin mRNA translation to levels observed in ductus cells.

Original languageEnglish (US)
Pages (from-to)3070-3082
Number of pages13
JournalJournal of Clinical Investigation
Volume100
Issue number12
DOIs
StatePublished - Dec 15 1997

Keywords

  • Cell migration
  • Ductus arteriosus
  • Extracellular matrix protein
  • Protein purification
  • Transfection

ASJC Scopus subject areas

  • Medicine(all)

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